Alzheimer's antipsychotic drugs "are not the answer for most," report says

Drugs widely prescribed to control agitation, aggression, hallucinations or delusions in Alzheimer's patients provided few, if any, benefits and carried severe side effects, according to a large study released Wednesday.

The findings of the federally funded clinical trial challenged conventional wisdom about the medications and painted a grim picture of the state of treatment of Alzheimer's disease.

"We need a new generation of drugs for these very serious behaviors," said Dr. Thomas Insel, director of the National Institute of Mental Health, which paid for the study. "These existing drugs are not the answer for most."

Alzheimer's disease is a disorder of the brain's nerve cells that progressively impairs memory, thinking and behavior. An estimated 4.5 million Americans have the disease, most of them over 65.

In the later stages of the illness, many patients experience severe personality changes and psychotic symptoms that pose huge challenges to caregivers. Those changes are often the determining factor in a family's decision to place a relative with Alzheimer's disease in a nursing home.

No drugs have been approved to treat these symptoms, but some studies have suggested that antipsychotic drugs developed for treating schizophrenia may help.

The drugs carry a "black box" warning, the strongest required by the Food and Drug Administration, about an increased risk of death in Alzheimer's patients.

The latest study, conducted at 33 university and hospital clinics and nine doctor's offices in the U.S., set out to assess the effectiveness of antipsychotics Zyprexa, Seroquel and Risperdal.

A total of 421 patients displaying moderate to severe psychotic symptoms, agitation or aggression were randomly assigned to receive either a placebo or an antipsychotic drug for up to 36 weeks. All patients either lived at home or at an assisted-living facility.

The trial attempted to mimic real-world conditions, measuring effectiveness by how long patients took the drug before quitting because they could not tolerate the side effect or saw no improvement.

On average, patients stopped taking their pills after about eight weeks, about the same duration as those taking a placebo.

Depending on the drug, 37 percent to 50 percent of patients discontinued their pills because they weren't working, and up to 24 percent stopped taking them because of side effects, such as drowsiness, weight gain and confusion.

All told, 82 percent of patients quit their medications.

The findings, reported in the New England Journal of Medicine, were unexpected, said lead author Dr. Lon Schneider of the University of Southern California.

"We thought we would see advantages with the drugs," he said. "From a big-picture point of view ... we are not gaining any effectiveness with these medications."

Despite the discouraging results, Schneider said the drugs had a role in treating some of the worst symptoms of Alzheimer's disease. The study hinted that some individual patients might benefit from the pills, he said.

"The message from this study cannot be that the drugs are not useful," he said. But doctors should change or discontinue medications if patients have side effects or don't improve in a matter of weeks, he said.

Dr. Claudia Kawas of the University of California, Irvine, who was not involved in the study, predicted that doctors would continue to use the drugs because there were no alternatives.

"The behavioral problems of Alzheimer's disease are huge," Kawas said. "To my mind, this study says these are powerful drugs and, if given in high enough doses to do any good, there are going to be side effects."

The study was the latest to reveal shortcomings in antipsychotic medications. An earlier trial, also federally funded, found the medications provided little benefit for schizophrenia patients and were no better than an older, cheaper drug, clozipine. That drug was not included in the Alzheimer's trial because it is not used to treat the disease.